Showing papers in "Nature Reviews Microbiology in 2004"
TL;DR: It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments.
Abstract: Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.
6,170 citations
TL;DR: Few microorganisms are as versatile as Escherichia coli; it can also be a highly versatile, and frequently deadly, pathogen.
Abstract: Few microorganisms are as versatile as Escherichia coli. An important member of the normal intestinal microflora of humans and other mammals, E. coli has also been widely exploited as a cloning host in recombinant DNA technology. But E. coli is more than just a laboratory workhorse or harmless intestinal inhabitant; it can also be a highly versatile, and frequently deadly, pathogen. Several different E. coli strains cause diverse intestinal and extraintestinal diseases by means of virulence factors that affect a wide range of cellular processes.
4,583 citations
TL;DR: Root colonization by Trichoderma spp.
Abstract: Trichoderma spp. are free-living fungi that are common in soil and root ecosystems. Recent discoveries show that they are opportunistic, avirulent plant symbionts, as well as being parasites of other fungi. At least some strains establish robust and long-lasting colonizations of root surfaces and penetrate into the epidermis and a few cells below this level. They produce or release a variety of compounds that induce localized or systemic resistance responses, and this explains their lack of pathogenicity to plants. These root-microorganism associations cause substantial changes to the plant proteome and metabolism. Plants are protected from numerous classes of plant pathogen by responses that are similar to systemic acquired resistance and rhizobacteria-induced systemic resistance. Root colonization by Trichoderma spp. also frequently enhances root growth and development, crop productivity, resistance to abiotic stresses and the uptake and use of nutrients.
3,261 citations
TL;DR: A review of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection, updates the reader on these concepts and the topical questions in the field.
Abstract: Phagocyte-derived reactive oxygen and nitrogen species are of crucial importance for host resistance to microbial pathogens. Decades of research have provided a detailed understanding of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection. However, differences of opinion remain with regard to their host specificity, cell biology, sources and interactions with one another or with myeloperoxidase and granule proteases. More than a century after Metchnikoff first described phagocytosis, and more than four decades after the discovery of the burst of oxygen consumption that is associated with microbial killing, the seemingly elementary question of how phagocytes inhibit, kill and degrade microorganisms remains controversial. This review updates the reader on these concepts and the topical questions in the field.
1,476 citations
TL;DR: This work has shown that a constraint-based reconstruction and analysis approach provides a biochemically and genetically consistent framework for the generation of hypotheses and the testing of functions of microbial cells.
Abstract: Microbial cells operate under governing constraints that limit their range of possible functions. With the availability of annotated genome sequences, it has become possible to reconstruct genome-scale biochemical reaction networks for microorganisms. The imposition of governing constraints on a reconstructed biochemical network leads to the definition of achievable cellular functions. In recent years, a substantial and growing toolbox of computational analysis methods has been developed to study the characteristics and capabilities of microorganisms using a constraint-based reconstruction and analysis (COBRA) approach. This approach provides a biochemically and genetically consistent framework for the generation of hypotheses and the testing of functions of microbial cells.
1,102 citations
TL;DR: Progress has been made in elucidating the molecular, biochemical, chemical and genetic bases of magnetosome formation and understanding how these unique intracellular organelles function.
Abstract: Magnetotactic bacteria were discovered almost 30 years ago, and for many years and many different reasons, the number of researchers working in this field was few and progress was slow. Recently, however, thanks to the isolation of new strains and the development of new techniques for manipulating these strains, researchers from several laboratories have made significant progress in elucidating the molecular, biochemical, chemical and genetic bases of magnetosome formation and understanding how these unique intracellular organelles function. We focus here on this progress.
1,009 citations
TL;DR: Recent lessons that have been learned from pathogenicity islands in pathogenic microorganisms are discussed and how they apply to the role of genomic islands in commensal, symbiotic and environmental bacteria are discussed.
Abstract: Horizontal gene transfer is an important mechanism for the evolution of microbial genomes. Pathogenicity islands — mobile genetic elements that contribute to rapid changes in virulence potential — are known to have contributed to genome evolution by horizontal gene transfer in many bacterial pathogens. Increasing evidence indicates that equivalent elements in non-pathogenic species — genomic islands — are important in the evolution of these bacteria, influencing traits such as antibiotic resistance, symbiosis and fitness, and adaptation in general. This review discusses the recent lessons that have been learned from pathogenicity islands in pathogenic microorganisms and how they apply to the role of genomic islands in commensal, symbiotic and environmental bacteria.
1,007 citations
TL;DR: The ability of microorganisms to use nitrogen gas as the sole nitrogen source and engage in symbioses with host plants confers many ecological advantages, but also incurs physiological penalties because the process is oxygen sensitive and energy dependent.
Abstract: Some bacteria have the remarkable capacity to fix atmospheric nitrogen to ammonia under ambient conditions, a reaction only mimicked on an industrial scale by a chemical process that requires high temperatures, elevated pressure and special catalysts. The ability of microorganisms to use nitrogen gas as the sole nitrogen source and engage in symbioses with host plants confers many ecological advantages, but also incurs physiological penalties because the process is oxygen sensitive and energy dependent. Consequently, biological nitrogen fixation is highly regulated at the transcriptional level by sophisticated regulatory networks that respond to multiple environmental cues.
979 citations
TL;DR: Bacteria use their genetic material with great effectiveness to make the right products in the correct amounts at the appropriate time, but for reasons of economy, the key step to regulate is the initiation of RNA-transcript formation.
Abstract: Bacteria use their genetic material with great effectiveness to make the right products in the correct amounts at the appropriate time. Studying bacterial transcription initiation in Escherichia coli has served as a model for understanding transcriptional control throughout all kingdoms of life. Every step in the pathway between gene and function is exploited to exercise this control, but for reasons of economy, it is plain that the key step to regulate is the initiation of RNA-transcript formation.
955 citations
TL;DR: Although 'diseases of affluence' are increasing in developing countries, infectious diseases still impose the greatest health burden and simple, accurate and stable diagnostic tests are essential to combat these diseases.
Abstract: Although 'diseases of affluence', such as diabetes and cardiovascular disease, are increasing in developing countries, infectious diseases still impose the greatest health burden. Annually, just under 1 million people die from malaria, 4.3 million from acute respiratory infections, 2.9 million from enteric infections and 5 million from AIDS and tuberculosis. Other sexually transmitted infections and tropical parasitic infections are responsible for hundreds of thousands of deaths and an enormous burden of morbidity. More than 95% of these deaths occur in developing countries. Simple, accurate and stable diagnostic tests are essential to combat these diseases, but are usually unavailable or inaccessible to those who need them.
860 citations
TL;DR: Surprisingly, certain microorganisms that grow at neutral pH have elegantly regulated systems that enable survival during excursions into acidic environments, and the best-characterized acid-resistance system is found in E. coli.
Abstract: Gastrointestinal pathogens are faced with an extremely acidic environment. Within moments, a pathogen such as Escherichia coli O157:H7 can move from the nurturing pH 7 environment of a hamburger to the harsh pH 2 milieu of the stomach. Surprisingly, certain microorganisms that grow at neutral pH have elegantly regulated systems that enable survival during excursions into acidic environments. The best-characterized acid-resistance system is found in E. coli.
TL;DR: How pathogens compete with the host for iron, and also how the host uses iron to counteract this threat is discussed.
Abstract: The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. It is also a pivotal component of the innate immune response through its role in the generation of toxic oxygen and nitrogen intermediates. During evolution, the shared requirement of micro- and macroorganisms for this important nutrient has shaped the pathogen-host relationship. Here, we discuss how pathogens compete with the host for iron, and also how the host uses iron to counteract this threat.
TL;DR: The goal of any anti-infective therapy is to administer a dose of drug that has an acceptably high probability of achieving the desired therapeutic effect balanced with an acceptable low probability of toxicity.
Abstract: Antimicrobial pharmacodynamics is the discipline that integrates microbiology and pharmacology, with the aim of linking a measure of drug exposure, relative to a measure of drug potency for the pathogen in question, to the microbiological or clinical effect achieved. The delineation of such relationships allows the drug dose to be chosen in a rational manner, so that the desired effect (for example, the maximal bactericidal effect) can be achieved in a large proportion of the intended patient population. Ultimately, the goal of any anti-infective therapy is to administer a dose of drug that has an acceptably high probability of achieving the desired therapeutic effect balanced with an acceptably low probability of toxicity. Appropriate use of the latest pharmacodynamic modelling approaches can minimize the emergence of resistance and optimize the outcome for patients.
TL;DR: The current knowledge of DNA transport during transformation is reviewed, and proteins related to those involved in the assembly of type IV pili and type II secretion systems are reviewed.
Abstract: Naturally competent bacteria are able to take up exogenous DNA and undergo genetic transformation. The transport of DNA from the extracellular milieu into the cytoplasm is a complex process, and requires proteins that are related to those involved in the assembly of type IV pili and type II secretion systems, as well as a DNA translocase complex at the cytoplasmic membrane. Here, we will review the current knowledge of DNA transport during transformation.
TL;DR: Targeted STD detection and treatment should have a central role in HIV prevention in these emerging epidemics, especially in China, eastern Europe and Russia.
Abstract: Factors that increase transmission
Factors that increase susceptibility
STDs and HIV transmission
STDs and community-based studies
More than 42 million people worldwide are now infected with HIV, in spite of sustained prevention activities. Although the spread of HIV has been primarily sexual, epidemiological studies have indicated that the efficiency of the spread of HIV is poor, perhaps as infrequently as 1 in every 1,000 episodes of sexual intercourse. However, sexually transmitted diseases (STDs) that cause ulcers or inflammation greatly increase the efficiency of HIV transmission — by increasing both the infectiousness of, and the susceptibility to HIV infection. STDs might be particularly important in the early stages of a localized HIV epidemic, when people with risky sexual behaviour are most likely to become infected. In China, eastern Europe and Russia, there has been a remarkable increase in the incidence of STDs in recent years, and this is reflected in the rapid increase in the spread of HIV in these areas. Targeted STD detection and treatment should have a central role in HIV prevention in these emerging epidemics.
TL;DR: Plin structures that have been solved using X-ray crystallography and nuclear magnetic resonance, together with models for pilus architectures inferred from electron microscopy, fibre diffraction and computation, have established a molecular basis for assembly and multi-functionality, with implications for therapeutic interventions.
Abstract: Type IV pili are remarkably strong, flexible filaments with varied roles in bacterial pathogenicity. All Gram-negative bacterial surfaces have type IV pili, which are polymeric assemblies of the protein pilin that evoke the host immune response and are potential drug and vaccine targets. Pilin structures that have been solved using X-ray crystallography and nuclear magnetic resonance, together with models for pilus architectures inferred from electron microscopy, fibre diffraction and computation, have established a molecular basis for assembly and multi-functionality, with implications for therapeutic interventions.
TL;DR: Similar to winnowing during a harvest, the symbiosis between the squid Euprymna scolopes and its luminous bacterial symbiont Vibrio fischeri involves a step-wise elimination of potential interlopers that ensures separation of the 'grain' from the 'chaff'.
Abstract: Most symbiotic associations between animals and microorganisms are horizontally transmitted — the microorganisms are acquired from the environment by each generation of the host. How are exclusive partnerships established in the context of the thousands of other microbial species that are present in the environment? Similar to winnowing during a harvest, the symbiosis between the squid Euprymna scolopes and its luminous bacterial symbiont Vibrio fischeri involves a step-wise elimination of potential interlopers that ensures separation of the 'grain' from the 'chaff'.
TL;DR: The evidence that nitrate-reducing commensals have a true symbiotic role in mammals and facilitate a previously unrecognized but potentially important aspect of the nitrogen cycle is considered.
Abstract: Nitrate is generally considered a water pollutant and an undesirable fertilizer residue in the food chain Research in the 1970s indicated that, by reducing nitrate to nitrite, commensal bacteria might be involved in the pathogenesis of gastric cancers and other malignancies, as nitrite can enhance the generation of carcinogenic N-nitrosamines More recent studies indicate that the bacterial metabolism of nitrate to nitrite and the subsequent formation of biologically active nitrogen oxides could be beneficial Here, we will consider the evidence that nitrate-reducing commensals have a true symbiotic role in mammals and facilitate a previously unrecognized but potentially important aspect of the nitrogen cycle
TL;DR: Several anabolic pathways for the parasite plastid are reconstructed that are fundamentally different to the analogous pathways in the human host and are potentially good targets for drug development.
Abstract: Discovery of a relict chloroplast (the apicoplast) in malarial parasites presented new opportunities for drug development The apicoplast – although no longer photosynthetic – is essential to parasites Combining bioinformatics approaches with experimental validation in the laboratory, we have identified more than 500 proteins predicted to function in the apicoplast By comparison with plant chloroplasts, we have reconstructed several anabolic pathways for the parasite plastid that are fundamentally different to the analogous pathways in the human host and are potentially good targets for drug development Products of these pathways seem to be exported from the apicoplast and might be involved in host-cell invasion
TL;DR: The mechanisms of disease emergence that are related to the host-range specificity of selected mosquito-borne alphaviruses and flaviviruses are reviewed.
Abstract: Many pandemics have been attributed to the ability of some RNA viruses to change their host range to include humans. Here, we review the mechanisms of disease emergence that are related to the host-range specificity of selected mosquito-borne alphaviruses and flaviviruses. We discuss viruses of medical importance, including Venezuelan equine and Japanese encephalitis viruses, dengue viruses and West Nile viruses.
TL;DR: The nature of the host immune response to this type of infection and the balance between clearance of the pathogen and avoidance of damage to host tissues are discussed.
Abstract: Persistent bacterial infections involving Mycobacterium tuberculosis, Salmonella enterica serovar Typhi (S. typhi) and Helicobacter pylori pose significant public-health problems. Multidrug-resistant strains of M. tuberculosis and S. typhi are on the increase, and M. tuberculosis and S. typhi infections are often associated with HIV infection. This review discusses the strategies used by these bacteria during persistent infections that allow them to colonize specific sites in the host and evade immune surveillance. The nature of the host immune response to this type of infection and the balance between clearance of the pathogen and avoidance of damage to host tissues are also discussed.
TL;DR: The possibility that horizontal gene transfer expands the repertoire of protein–protein interactions that nucleoid-associated proteins can engage in, with potentially profound consequences for the global gene-expression profile of the cell is raised.
Abstract: The effect of the bacterial heat-stable nucleoid-structuring (H-NS) protein on gene expression is overwhelmingly negative and extends throughout the genome, pointing to an almost universal role for this nucleoid-associated protein as a transcriptional repressor. Its ability to exert widespread effects on gene expression probably reflects the fact that it binds to curved DNA, which is commonly found at promoters. H-NS and related proteins can engage in both homologous and heterologous protein–protein interactions. Recent data show that the genes that encode H-NS-like proteins can be carried on mobile genetic elements. This raises the possibility that horizontal gene transfer expands the repertoire of protein–protein interactions that nucleoid-associated proteins can engage in, with potentially profound consequences for the global gene-expression profile of the cell.
TL;DR: Advances in the understanding of how viral entry proteins interact with their host-cell receptors and undergo conformational changes that lead to entry offer unprecedented opportunities for the development of novel therapeutics and vaccines.
Abstract: Viruses have evolved to enter cells from all three domains of life — Bacteria, Archaea and Eukaryotes. Of more than 3,600 known viruses, hundreds can infect human cells and most of those are associated with disease. To gain access to the cell interior, animal viruses attach to host-cell receptors. Advances in our understanding of how viral entry proteins interact with their host-cell receptors and undergo conformational changes that lead to entry offer unprecedented opportunities for the development of novel therapeutics and vaccines.
TL;DR: The recent completion of the whole-genome sequence of the perchlorate-reducing microorganism Dechloromonas aromatica offers further insight into the evolution and regulation of this unique metabolic pathway.
Abstract: It is less than 7 years since perchlorate, a predominantly man-made toxic anion, was first identified as a significant water contaminant throughout the United States. Owing to its solubility and non-reactivity, bioremediation was targeted as the most promising solution for the problem of perchlorate contamination. Since 1996, concerted efforts have resulted in significant advances in our understanding of the microbiology, biochemistry and genetics of the microorganisms that are capable of reductively transforming perchlorate into innocuous chloride. The recent completion of the whole-genome sequence of the perchlorate-reducing microorganism Dechloromonas aromatica offers further insight into the evolution and regulation of this unique metabolic pathway. Several in situ and ex situ bioremediative processes have been engineered, and many monitoring tools that are based on immunology, molecular biology and stable isotope content are now available. As such, the rapid scientific response to this emerging contaminant offers great hope for its successful elimination from contaminated environments in the future.
TL;DR: Francisella tularensis is a highly infectious aerosolizable intracellular pathogen that is capable of causing a debilitating or fatal disease with doses as low as 25 colony-forming units, and there is no licensed vaccine available.
Abstract: Francisella tularensis is a highly infectious aerosolizable intracellular pathogen that is capable of causing a debilitating or fatal disease with doses as low as 25 colony-forming units. There is no licensed vaccine available. Since the 1950s there has been concern that F. tularensis could be used as a biological threat agent, and it has received renewed attention recently owing to concerns about bioterrorism. The International Conference on Tularaemia in 2003 attracted more than 200 delegates, twice the number of participants as previous meetings. This is a reflection of the increased funding of research on this pathogen, particularly in the United States.
TL;DR: Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of antibody-based therapy for the prevention and treatment of infectious diseases.
Abstract: Antibody-based therapies are currently undergoing a renaissance. After being developed and then largely abandoned in the twentieth century, many antibody preparations are now in clinical use. However, most of the reagents that are available target non-infectious diseases. Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that antibody-based therapies are the only means to provide immediate immunity against biological weapons. Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of antibody-based therapy for the prevention and treatment of infectious diseases.
TL;DR: Rapid advances in cellulosome research are providing basic information for the development of both in vitro and in vivo systems to achieve such goals as conversion of cellulosic biomass into sugars by cellulosomes could result in the production of high-value products from inexpensive renewable resources.
Abstract: Cellulose, the main structural component of plant cell walls, is the most abundant carbohydrate polymer in nature. Although abundant, it is extremely difficult to degrade, as it is insoluble and is present as hydrogen-bonded crystalline fibres. Anaerobic microorganisms have evolved a system to break down plant cell walls that involves the formation of a large extracellular enzyme complex called the cellulosome, which consists of a scaffolding protein and many bound cellulases. Cellulosomes have many potential biotechnological applications as the conversion of cellulosic biomass into sugars by cellulosomes could result in the production of high-value products such as ethanol or organic acids from inexpensive renewable resources. Rapid advances in cellulosome research are providing basic information for the development of both in vitro and in vivo systems to achieve such goals.
TL;DR: The molecular mechanisms of the avoidance and subversion of autophagy by microorganisms will be the subject of much future research, not only to study their roles in the replication of these microorganisms, but also because they will provide — as bacteria and viruses so often have — unique tools to study the cellular process itself.
Abstract: Intracellular bacteria and viruses must survive the vigorous antimicrobial responses of their hosts to replicate successfully. The cellular process of autophagy — in which compartments bound by double membranes engulf portions of the cytosol and then mature to degrade their cytoplasmic contents — is likely to be one such host-cell response. Several lines of evidence show that both bacteria and viruses are vulnerable to autophagic destruction and that successful pathogens have evolved strategies to avoid autophagy, or to actively subvert its components, to promote their own replication. The molecular mechanisms of the avoidance and subversion of autophagy by microorganisms will be the subject of much future research, not only to study their roles in the replication of these microorganisms, but also because they will provide — as bacteria and viruses so often have — unique tools to study the cellular process itself.
TL;DR: The population and evolutionary dynamics of bacterial–phage interactions that are relevant to phage therapy and prophylaxis are reviewed and illustrated with computer simulations.
Abstract: Following a sixty-year hiatus in western medicine, bacteriophages (phages) are again being advocated for treating and preventing bacterial infections. Are attempts to use phages for clinical and environmental applications more likely to succeed now than in the past? Will phage therapy and prophylaxis suffer the same fates as antibiotics--treatment failure due to acquired resistance and ever-increasing frequencies of resistant pathogens? Here, the population and evolutionary dynamics of bacterial-phage interactions that are relevant to phage therapy and prophylaxis are reviewed and illustrated with computer simulations.
TL;DR: Advances in biochemical analyses are revealing a range of elegant solutions that have evolved to allow bacteria to sense different redox signals, which are vital to all organisms.
Abstract: Redox reactions pervade living cells. They are central to both anabolic and catabolic metabolism. The ability to maintain redox balance is therefore vital to all organisms. Various regulatory sensors continually monitor the redox state of the internal and external environments and control the processes that work to maintain redox homeostasis. In response to redox imbalance, new metabolic pathways are initiated, the repair or bypassing of damaged cellular components is coordinated and systems that protect the cell from further damage are induced. Advances in biochemical analyses are revealing a range of elegant solutions that have evolved to allow bacteria to sense different redox signals.